Neurodegenerative diseases: Therapeutic targets and reagents

Neurodegeneration is a neurological condition characterized by progressive atrophy and permanent neuronal damage. Two of the most prevalent neurodegenerative disorders are Alzheimer’s disease (AD) and Parkinson’s disease (PD).

GDNF, NGF, and BDNF are growth factors that help neurons survive, maintain, and regenerate, making them potential therapies for neurodegenerative illnesses.

Neurodegenerative diseases: therapeutic targets and reagents

Figure 1. Neuron Specificity Image Credit: Sino Biological Inc.

Clinical studies for GDNF (a treatment for Parkinson’s disease), NGF (a treatment for Alzheimer’s disease), and BDNF (a treatment for both AD and PD) are now underway.

Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and Rett syndrome are among the less frequent neurodegenerative illnesses that potentially benefit from therapies targeting neurotrophic factors and related receptors.

Neurotrophins and receptors

Neurotrophins are growth factors required for neuron survival, development and maintenance. NGF, BDNF, neurotrophin 3, and neurotrophin 4 are members of the neurotrophin family.

They can induce neurotrophic or pro-apoptotic signaling by binding to certain Trk receptors with high affinity and p75NTR with low affinity, respectively. NGF attaches to TrkA, while BDNF and neurotrophin 4 attach to TrkB and TrkC, respectively.

In Alzheimer’s disease, NGF, BDNF, and all receptors are candidates for treatment. BDNF can potentially be used to treat Parkinson’s disease.

NGF (nerve growth factor)

NGF is the first member of the neurotrophin family to be found. Specific neurons rely on it for life, development and maintenance.

Human NGF protein

11050-HNAC

  • Expressed Host: CHO Stable Cells
  • Activity: TF-1 human erythroleukemic cells were used in a cell proliferation experiment.
  • Purity: >95%

Neurodegenerative diseases: therapeutic targets and reagents

Image Credit: Sino Biological Inc.

BDNF (brain derived neurotrophic factor)

Sensory neurons, retinal ganglia, some cholinergic neurons, spinal motor neurons, and certain dopaminergic neurons all benefit from BDNF.

Mouse BDNF Protein

50240-M08H

  • Purity: >95%
  • Expressed Host: HEK293 Cells

Neurodegenerative diseases: therapeutic targets and reagents

Image Credit: Sino Biological Inc.

Neurotrophin 3/NT3

Human NT3 Protein

  • Expressed Host: E. coli
  • Activity: Binding capacity to human TrkB in a functional ELISA.
  • Purity: > 90%

Neurodegenerative diseases: therapeutic targets and reagents

Image Credit: Sino Biological Inc.

Neurotrophin 4/NT4

10265-HNAE

  • Purity: >95%
  • Expressed Host: HEK293 Cells

Trk receptors

Table 1. Source: Sino Biological Inc.

Cat# Molecule Species Expressed Host Purity Tag Activity
11073-H03H TrkA Human HEK293 Cells >98% C-hFc & His Active
11073-H07E1 TrkA Human E. coli >97% N-His Active
51103-M02H TrkA Mouse HEK293 Cells >90% C-hFc Active
51103-M08H TrkA Mouse HEK293 Cells >95% C-His Active
70101-D01H TrkA Canine HEK293 Cells >90% N-hFc Active
70101-D07H TrkA Canine HEK293 Cells >95% N-His Active
80404-R02H TrkA Rat HEK293 Cells >95% C-hFc Active
80404-R08H TrkA Rat HEK293 Cells >95% C-His Active
10047-H03H TrkB Human HEK293 Cells >90% C-hFc & His Active
10047-H08H TrkB Human HEK293 Cells >97% C-His Active
50132-M08H TrkB Mouse HEK293 Cells >98% C-His Active
70035-D08H TrkB Canine HEK293 Cells >95% C-His Active
80243-R08H TrkB Rat HEK293 Cells >95% C-His Active
10048-H03H TrkC Human HEK293 Cells >98% C-hFc & His Active
10048-H08H TrkC Human HEK293 Cells >95% C-His Active
50320-M08H TrkC Mouse HEK293 Cells >95% C-His Active

 

Low affinity common receptor to neurotrophins: p75NTR

Human p75NTR Protein

13184-H02H

  • Purity: >95%
  • Expressed Host: HEK293 Cell
  • Activity: ED50 is 0.5–3 g/mL in the presence of 4 ng/mL Recombinant Human NGF and inhibits NGF-dependent proliferation of TF-1 human erythroleukemic cells.

Mouse p75NTR Protein

50971-M02H

  • Purity: >90%
  • Expressed Host: HEK293 Cell
  • Activity: TF-1 human erythroleukemic cells’ NGF-dependent proliferation is inhibited. When 2 ng/mL recombinant mouse NGF is present, the ED50 is 0.5–3 g/mL.

GDNF & receptor complex

GDNF, or glial cell line-derived neurotrophic factor, is important for motor neuron survival and axon expansion. It is being tested in clinical studies as a possible treatment for Parkinson’s. Drugs similar to GFL are under development to treat neuropathic pain and addiction.

The GDNF family of ligands (GFLs) also includes neurturin (NRTN), artemin (ARTN), and persephin (PERS) (PSPN). These compounds bind to the proteins GFRA1, GFRA2, GFRA3, and GFRA4.

The activation of the RET tyrosine kinase receptor by the GDNF/GFRA1 complex leads to cell survival, proliferation and development via the MAPK/ERK or PI3K/Akt pathways. GDNF/GFRA1 also binds to NCAM and causes axonal growth. GDNF can also work in tandem with other growth factors, such as transforming growth factor-beta (TGF-beta).

Sino Biological has created recombinant GDNF and GFRA1 proteins and antibodies from a variety of animals, including humans, mice, cynomolgus, rabbits, rats and dogs.

GDNF is an important factor in the treatment of Parkinson’s disease. As a common signaling receptor shared by GDNF family ligands, GDNF binds to GFR1 and Ret protein. Sino Biological has created bioactive recombinant growth factors from human, mouse, cynomolgus, rhesus, rat, and canine species.

Recombinant GDNF and GFRA1 proteins

Human GDNF protein

10561-HNCH

Neurodegenerative diseases: therapeutic targets and reagents

Binding ability by ELISA. Immobilized human GFRA1 (Cat:10330-H02H) at 10 μg/mL (100 μL/well) can bind GDNF. Image Credit: Sino Biological Inc.

Rat GDNF protein

80050-R07B

  • Purity: >95%
  • Expressed Host: Insect Cell
  • Activity:
    1. Bind rat GFRA1
    2. Cell Proliferation

Canine GDNF protein

70255-D01H

  • Purity: >90%
  • Expressed Host: HEK293 Cell

Neurodegenerative diseases: therapeutic targets and reagents

Figure 2. GDNF ligand dimer binds to two GFRα receptors and dimerizes two RET receptors. Image Credit: Sino Biological Inc.

More GFRα1 proteins

Table 2. Source: Sino Biological Inc.

Cat# Species Expressed Host Tag Purity Activity
10330-H02H Human HEK293 Cells hFc >90% Active
10330-H08H Human HEK293 Cells His >98% Active
50171-M08H Mouse HEK293 Cells His >98% Active
70062-D08H Canine HEK293 Cells His >95%  
80021-R02H Rat HEK293 Cells hFc >90% Active
80021-R08H Rat HEK293 Cells His >97% Active

Other related proteins

  • ARTN
  • GFRA2
  • GFRA3
  • RET
  • NCAM
  • TGF-beta

Antibodies for GDNF and GFRA1

Sino Biological has created a GDNF and GFRA1 antibody panel that can be utilized in WB, IF, ELISA, and ICC.

Anti-GFRA1 rabbit monoclonal antibody

(Cat#: 50171-R009)

Neurodegenerative diseases: therapeutic targets and reagents

Immunofluorescence Staining of GDNF in U251MG Cells. Image Credit: Sino Biological Inc.

Anti-GFRA1 rabbit monoclonal antibody

(Cat#: 50171-R009)

Neurodegenerative diseases: therapeutic targets and reagents

Immunochemical Staining of Mouse GFRA1 in Mouse Kidney Cells. Image Credit: Sino Biological Inc.

GDNF superfamily & receptors

In the embryonic and adult central nervous systems, GDNF superfamily proteins (artemin/ARTN, neurturin/NRTN, and persephin/PSPN) have protective and restorative actions (CNS). GFR1, GFR2, GFR3, and GFR4 are bounded by GDNF, Neurturin, Artemin, and Persephin, respectively.